Urinary acidification is needed for normal acid-base homeostasis, and disorders of acidification are important causes of morbidity in chronic renal failure and other kidney diseases. The long term objectives of this proposal are to examine mechanisms for regulation of the renal proton pump at several levels of control. The specific aims are: 1) To determine the primary structure of subunits from the bovine kidney proton pump. 2) To use bovine kidney proton pump DNA probes to identify classes of proton pump mRNAs in the rat kidney, and evaluate their functional significance. 3) To examine factors that affect kidney proton pump mRNAs in cultured cells. 4) To examine the genomic structure of the rat kidney proton pump. 5) To generate monoclonal antibodies to extracellular domains of the renal proton pump for studying its surface density. 6) To examine the possible role of cytosolic proteins in regulating proton pump enzymatic activity. These studies will enhance our understanding of how urinary acidification is regulated.